The purpose of this project is to develop diagnostic tools that will enable population-based early cancer detection. This effort arises out of a long-term collaboration with investigators at Hopkins that led to a report in 1988 that showed we could improve the diagnosis of early lung cancer using a sputum-based immunodetection assay. We have continued that work by conducting two prospective validation trials. The initial results of those studies have been published and suggest that the test correctly finds at least two thirds of the lung cancer cases well in advance of any other evidence of the cancer. To determine if this approach is appropriate for broader application, we are working under a CRADA mechanism with the company, Chiron (Bayer Diagnostics), Johns Hopkins, the University of South Florida as well as the institutions of the Lung Cancer Early Detection Working Group to refine this diagnostic technology for population-based application. In a series of papers, we describe the potential basis for the success of this assay. We have found that the target marker recognized by the antibody is the molecule, heterogeneous nuclear, ribonucleoprotein A2/B1 (hnRNP). The distribution of that marker is associated with a significantly more frequent occurrence of other molecular events associated with lung cancer such as loss of portions of critical genes. We have also found that the timing and pattern of expression of hnRNP in developing lungs is consistent with this molecule playing a role in early lung development. Another group in England using this antibody for early lung cancer detection has recently reported diagnostic accuracy with the immunostaining approach similar to our previous studies. The English study will be published in Clinical Cancer Research. While work on understanding the biological basis for routine early lung cancer detection continues, progress is being made in developing the infrastructure to offer this test as a screening tool. A number of studies are being developed to validate this approach in early lung cancer detection. The instrumentation platform to conduct the high throughput cell analysis will be conducted using the approach developed by NeoPath for cervical smear analysis. Bayer Diagnostic and NeoPath have recently signed an agreement to jointly develop this capability to address this aspect of the CRADA effort. The ultimate goal of this development project is to identify useful and economical analytical tools that provide a comprehensive picture about the status of the carcinogen-exposed epithelium. The principal vehicle to validate the utility of this approach is the 14 center prospective diagnostic trial being conducted under this trial. The thoracic oncology centers that are accruing curatively resected lung cancer patients have been very effective. The total number of patients on this study now is close to 1000 patients. With the need to capture 100 events in this study population to allow for a significant evaluation of this approach, this study could be completed over the next year. - molecular diagnostics, early cancer detection, cellular diagnostics, population-based screening, field carcinogenesis, - Human Subjects & Human Tissues, Fluids, Cells, etc.